Project Grant R01HL167731
- This $225,306 Project Grant award from the National Science Foundation (NSF) Biological Sciences program (CFDA 47.074) supports a collaborative research project between researchers at the University of Southern California (USC) and a German partner to investigate the long-term impact of early-life growth signals on adult hematopoietic (blood) stem cell function and selection. The key products and services to be delivered under this 3-year award include: 1) using stem cell transplantation and...
- This Project Grant from the National Heart, Lung and Blood Institute, part of the Department of Health and Human Services, provides $914,900 to Ship Of Theseus LLC under the Cardiovascular Diseases Research program (CFDA 93.837). The funding supports preclinical development of a nuclear-targeting biologic to safely increase stem cell expansion in vivo and accelerate recovery from neutropenia following chemotherapy and bone marrow transplant. Specifically, the grant will advance a patented mutant...
- This federal Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI), under the Cardiovascular Diseases Research program (CFDA 93.837), provides $299,781 to Mogling Bio Inc. to develop a therapeutic regimen that can attenuate aging of human hematopoietic stem cells (HSCs). The central goal is to validate the use of the drug CASIN to restore CDC42-regulated polarity and rejuvenate aged human HSCs ex vivo. This research aims to benefit bone marrow HSC transplant patients...
- Federal Grant Award Summary The National Heart, Lung, and Blood Institute (NHLBI) awarded The Leland Stanford Junior University a $758,539 Project Grant effective August 1, 2025, through May 31, 2030, under the Cardiovascular Diseases Research program (CFDA 93.837). This research initiative investigates the mechanistic pathways through which altered mitochondrial dynamics contribute to graft-versus-host disease (GVHD), the leading cause of non-relapse mortality following hematopoietic stem...
- This federal Project Grant award of $225,101 from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395) supports research to investigate the mechanisms underlying the increased risk of hematological malignancies in sickle cell disease patients. The key objectives of this 2-year project are to: 1) Perform experiments to understand how increased oxidative stress and DNA damage in hematopoietic stem and progenitor cells lead to the development of clonal...
- Federal Project Grant Award Summary The University of Texas Southwestern Medical Center received a $259,446 Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), effective July 23, 2025, with completion targeted for January 27, 2028. This grant funds research focused on understanding transplant relapse in myelodysplastic syndromes (MDS) through early detection of residual disease among hematopoietic stem...
- Federal Grant Award Summary The National Heart, Lung, and Blood Institute (NHLBI) awarded Columbia University's Health Sciences Division a $1,394,592 Project Grant under the Cardiovascular Diseases Research program (CFDA 93.837) on August 5, 2025, with completion targeted for March 31, 2026. This research initiative investigates epitranscriptomic regulation of hematopoietic stem cell (HSC) niche generation and regeneration, focusing on the role of N6-methyladenosine (M6A) mRNA modifications in...
- This five-year Project Grant, awarded by the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), provides $153,117 in obligated funding beginning August 1, 2025, through July 31, 2030. The award supports a physician-scientist's career development and independent research program focused on improving hematopoietic stem and progenitor cell (HSPC) transplantation outcomes through investigation of cellular crosstalk mechanisms between...
- Grant Award Summary Fred Hutchinson Cancer Center received a $1,326,626 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded May 15, 2025, with completion targeted for February 28, 2029. The research project, titled "DLK1 Regulates HSC Quiescence Through Phase Separation Mediated Inhibition of Receptor Signaling," focuses on investigating the role of Delta-like Homologue 1 (DLK1) protein in...
- Federal Grant Award Summary The National Heart, Lung, and Blood Institute (NHLBI) awarded The Trustees of Columbia University in the City of New York a Project Grant of $761,262 under the Cardiovascular Diseases Research program (CFDA 93.837), with performance from September 1, 2025 through June 30, 2029. This award funds research aimed at defining the mechanisms by which intravenously administered bone marrow-derived mesenchymal stromal cells (BMSCs) protect against acute lung injury (ALI). The...
REGULATORY MECHANISMS OF HEMATOPOIETIC STEM CELL FUNCTIONS POST-TRANSPLANT - ABSTRACT HEMATOPOIETIC STEM CELLS (HSC) SUSTAIN THE PRODUCTION OF ALL BLOOD AND IMMUNE CELLS THROUGHOUT LIFE BY DIFFERENTIATING INTO ALL BLOOD LINEAGES AND REGENERATE LONG-LIVED HSC, IE SELF-RENEW. HOWEVER, ALTHOUGH HSC HAVE HIGH REGENERATIVE POTENTIAL, THE ACTUAL CAPACITY OF 'SELF-RENEWAL', IE REGENERATING A DAUGHTER CELL THAT HAS IDENTICAL PROPERTIES' IS LIMITED. HSC SUSTAIN INJURY AFTER BONE MARROW TRANSPLANTATION AND BECOME LESS FUNCTIONAL. A CLEAR UNDERSTANDING OF THE MECHANISM RESPONSIBLE FOR HSC FUNCTIONAL DECLINE WITH HSC TRANSPLANTATION IS STILL LACKING. THIS LACK OF KNOWLEDGE HAS HAMPERED OUR ABILITY TO MAINTAIN HSC FUNCTIONS THROUGH DIVISIONS AND IMPROVE HSCT OUTCOMES. THE OVERALL GOAL OF THIS GRANT APPLICATION IS TO UNDERSTAND THE MECHANISMS BEHIND HSC FUNCTIONAL DECLINE AFTER BONE MARROW TRANSPLANTATION. WE HAVE DISCOVERED THAT ONCE HSCS GET ACTIVATED, MITOCHONDRIA IRREVERSIBLY REMODEL AND DO NOT RETURN TO HOMEOSTATIC CONDITIONS. HSCS ACCUMULATE DYSFUNCTIONAL MITOCHONDRIA DUE TO A PROGRESSIVE DECLINE IN MITOCHONDRIAL QUALITY CONTROL MECHANISMS, INCLUDING REDUCED MITOCHONDRIAL DYNAMISM SUCH THAT HSCS CARRY MITOCHONDRIA HAVE THAT ARE DIFFERENT IN SHAPE AND FUNCTIONS. MECHANISTICALLY, HSC LOSE MITOCHONDRIAL FISSION ACTIVITY [IE, LOSS OF THE FISSION REGULATOR DRP1 ACTIVITY], WHICH CAUSES A DECREASE IN HSC REGENERATIVE POTENTIAL. IN ADDITION, WE FOUND THAT HSC WITH HIGH REPOPULATION ACTIVITY IN VIVO HAVE HIGH LEVELS OF MITOPHAGY. IN CONTRAST MITOPHAGY IS DRASTICALLY REDUCED IN HSC AFTER TRANSPLANTATION. WE HYPOTHESIZE THAT MITOCHONDRIAL DEFECTS DRIVE HSC FUNCTIONAL DECLINE AFTER TRANSPLANTATION. THE MAIN OBJECTIVES OF THIS PROJECT ARE TO UNDERSTAND WHY ABNORMAL MITOCHONDRIA IN HSC ARE NOT REMOVED AFTER BONE MARROW TRANSPLANTATION AND THE IMPACT IT HAS ON HSC FUNCTIONS (AIM1). AIM2 WILL INVESTIGATE THE IMPACT OF ABNORMAL MITOCHONDRIA ON HSC METABOLISM WITH A FOCUS THE MITOCHONDRIAL RETROGRADE SIGNALING ATF4-ON CARBON/FOLATE PATHWAY. WE WILL TEST EFFECT OF METABOLITE SUPPLEMENTATION IN AMELIORATING HSC FUNCTIONS IN VIVO DURING BONE MARROW TRANSPLANTATION, USING BOTH MURINE BONE MARROW TRANSPLANTATION AND XENOTRANSPLANT MODEL OF HUMAN CD34+ INTO IMMUNODEFICIENT RECIPIENTS. THE PROPOSED STUDIES PROVIDE A UNIQUE OPPORTUNITY TO EXAMINE THE SPECIFIC CONTRIBUTION OF ABNORMAL MITOCHONDRIAL FUNCTIONS TO HSC FUNCTIONAL DECLINE DURING AND AFTER BONE MARROW TRANSPLANTATION. IT WILL INVESTIGATE THE NOVEL CONCEPT THAT HSCS ACCUMULATE DYSFUNCTIONAL MITOCHONDRIA THAT REPROGRAM THEIR METABOLISM DRIVING THEIR FUNCTIONAL DECLINE, WHICH MAY LEAD TO THE IDENTIFICATION OF NOVEL APPROACHES FOR PHARMACOLOGICAL INTERVENTION TO MAINTAIN HSC FUNCTIONS THROUGH DIVISIONS.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $647.6k | 6/6/25 | ||
| Not listed | $642.8k | 6/20/24 | ||
| Not listed | $642.8k | 6/20/24 |
GrantNumber | Description | Subgrantee | Prime Award | Dollars Obligated | Updated At |
|---|---|---|---|---|---|
OS00000908S | The Regents Of The University Of Colorado | Project Grant R01HL167731 | $41.5k | 7/24/25 |